Large cribriform growth pattern identifies ISUP grade 2 prostate cancer at high risk for recurrence and metastasis

Abstract

Invasive cribriform and intraductal carcinoma are associated with adverse clinical outcome in patients with Gleason score 7 prostate cancer. It is yet unclear whether invasive cribriform and intraductal carcinoma of the prostate both have independent prognostic value, or whether field size of invasive cribriform carcinoma has impact on disease outcome. Our objective was to determine the prognostic impact of intraductal and invasive cribriform prostate cancer histological subtypes in radical prostatectomies. We reviewed 420 prostatectomy specimens with ISUP grade 2 prostate cancer, assessed the percentages of Gleason grade 4 and tertiary 5, and performed immunohistochemistry for basal cells to discriminate intraductal from invasive cribriform growth. Small and large invasive cribriform fields were distinguished based on a diameter of at least twice the size of adjacent pre-existent normal glands. Clinicopathological parameters and biochemical recurrence-free survival were used as endpoints. Cribriform architecture was observed in 228 (54.3%) men, 103 (24.5%) of whom had intraductal, 194 (46.2%) small invasive, and 34 (8.1%) large invasive cribriform growth. Large invasive cribriform architecture was associated with older age (P < 0.001), higher percentage Gleason grade 4 (P = 0.001), extraprostatic expansion (P < 0.001), and more frequent lymph node metastases (P = 0.002), when compared with small invasive cribriform and/or intraductal carcinoma. Univariate analysis identified PSA, pT-stage, surgical margin status, and intraductal and invasive cribriform growth as significant predictors for biochemical recurrence-free survival. In multivariable Cox regression analysis, pT-stage (hazard ratio = 1.64, 95% CI: 1.02–2.63, P = 0.04), positive surgical margins (hazard ratio = 3.28, 95% CI: 2.06–5.23, P < 0.001), and large cribriform growth (hazard ratio = 4.36, 95% CI: 2.08–9.17, P < 0.001) were independent predictors for biochemical recurrence-free survival, while intraductal carcinoma, small cribriform growth, and percentage of Gleason grade 4 were not. In conclusion, large cribriform fields represent an aggressive subpattern of invasive cribriform prostate cancer and are an independent predictive factor for biochemical recurrence-free survival in ISUP grade 2 prostate cancer patients.

Improved Prostate Cancer Biopsy Grading by Incorporation of Invasive Cribriform and Intraductal Carcinoma in the 2014 Grade Groups

“…Diolombi and Epstein [22] found 0.6% pelvic lymph node metastasis among 3235 men with GG2 Pca at RP without stratification for CR/IDC. In another GG2 RP cohort, lymph node metastasis were present in 12/228 (5.3%) patients with CR/IDC but in none of 192 men without CR/IDC [23]. Studies comparing the interobserver variability of both models, however, still have to be performed.…”

Clinical outcome comparison of Grade Group 1 and Grade Group 2 prostate cancer with and without cribriform architecture at the time of radical prostatectomy

“…During the last decade, various studies demonstrated that GG2 patients with invasive cribriform and/or intraductal carcinoma have worse disease outcomes than those without 8,9,14,16,28,29 . Although it is generally accepted that GG2 patients have more aggressive disease than GG1 patients, it is unclear whether this is still the case when those with aggressive cribriform pathology are excluded.…”

“…Invasive and/or intraductal cribriform carcinoma, both also referred to as cribriform architecture, have been identified as pathological parameters for worse outcome in both biopsy and radical prostatectomy specimens 7–12 . Cribriform architecture has been associated with advanced tumour stage, biochemical recurrence, metastasis and disease‐specific death in GG2 patients 13–15 . Although patients with GG2 prostate cancer without cribriform architecture (GG2−) have favourable outcomes as compared with those with invasive and/or intraductal cribriform carcinoma (GG2+), it is unclear to what extent GG2− prostate cancer differs from GG1 prostate cancer.…”

Expansile cribriform Gleason pattern 4 has histopathologic and molecular features of aggressiveness and greater risk of biochemical failure compared to glomerulation Gleason pattern 4

“…In one study, the expansile cribriform pattern (Figure 1A) was associated with similar outcomes to Gleason pattern 5 carcinomas and was significantly linked to treatment failure, with a higher cumulative odds ratio of failure per added square millimeter of cribriform pattern than for any other type of Gleason pattern 4 4 . In another study that compared expansile cribriform to simple cribriform, the expansile cribriform pattern was associated with higher percentages of Gleason pattern 4, extraprostatic extension (EPE), and more frequent lymph node metastases, and was an independent predictor of BCR‐free survival 5 …”

“…The cribriform pattern, for example, has been associated with worse outcomes than other types of pattern 4 1,2 and is an independent parameter for biochemical recurrence (BCR) after prostatectomy 3 . Various studies have further subdivided the cribriform Gleason pattern 4 into two types, simple cribriform (also called small cribriform) and expansile cribriform (also called large cribriform), with the expansile cribriform pattern variously defined as large cribriform acini with greater than 12 lumen spaces 4 or as cribriform structures with a diameter of at least twice the size of adjacent normal glands 5 . In one study, the expansile cribriform pattern (Figure 1A) was associated with similar outcomes to Gleason pattern 5 carcinomas and was significantly linked to treatment failure, with a higher cumulative odds ratio of failure per added square millimeter of cribriform pattern than for any other type of Gleason pattern 4 4 .…”